Vaccines are a proven and effective approach for assuring widespread protection of large populations prior to or immediately following a bioterrorism attack. Our goal is to address two significant problems currently raised by bioterrorism threats: 1) the need for an easy method of mass vaccination and 2) the shortcomings of the current anthrax vaccine (NIAID "category A" agent) which requires needles and health professionals for administration, an extended vaccination schedule for protection (6 doses over 18 months) and the concern over adverse effects. To address this challenge, we have exploited the extensive safety record of the existing live, oral Salmonella Typhi Ty21a vaccine by utilizing it as a vector to develop a live oral vaccine carrier stably expressing rPA. We hypothesize that Ty21a is a suitable vaccine carrier for the stable expression of the rPA gene harbored on a low copy number plasmid. Further, we hypothesize that this vaccine can be formulated so that it will be safe, stable, and highly immunogenic and can be easily administered orally. The current proposal is aimed at completing the necessary final development steps (e.g. removal of antibiotic resistance gene from vector plasmid) and full characterization (genetic and microbiological) of the candidate prior to constructing a genetic seed bank and small-scale (5-10 liter) manufacture and lyophilization. Finally, the candidate will be studied for genetic stability, safety, immunogenicity and efficacy in a mouse model of anthrax disease. Successful completion of this Phase I SBIR will provide the foundation for development of an oral anthrax vaccine in a Phase II proposal, and for a platform technology for oral vaccines against multiple other infectious agents. PUBLIC HEALTH RELEVANCE: Anthrax bacteria produce spores that can be processed to become easily airborne. Vaccines are a proven and effective approach for assuring widespread protection of large populations prior to or immediately following a bioterrorism attack. Our goal is to address two significant problems currently raised by bioterrorism threats: 1) the need for an easy method of mass vaccination and 2) the shortcomings of the current anthrax vaccine (NIAID "category A" agent) which requires needles and health professionals for administration, an extended vaccination schedule for protection (6 doses over 18 months) and the concern over adverse effects. Further, we hypothesize that this vaccine can be formulated so that it will be safe, stable, and highly immunogenic and ultimately can be easily administered orally.